Abstract:
The review is devoted to the latest achievements in the design of dual action antibiotics — heterodimeric (chimeric) structures based on antibacterial agents of different classes (fluoroquinolones, anthracyclines, oxazolidines, macrolides and so on). Covalent binding can make the pharmacokinetic characteristics of these molecules more predictable and improve the penetration of each component into the cell. Consequently, not only does the drug efficacy increase owing to inhibition of two targets but also the resistance to one or both antibiotics can be overcome. The theoretical grounds of elaboration, design principles and methods for the synthesis of dual action antibiotics are considered. The structures are classified according to the type of covalent spacer (cleavable or not) connecting the moieties of two agents. Dual action antibiotics with a spacer that can be cleaved in a living cell are considered as dual action prodrugs. Data on the biological action of heterodimeric compounds are presented and structure–activity relationships are analyzed.
The bibliography includes 225 references.
Received: 20.02.2014
Bibliographic databases:
Document Type:
Article
Language: English
Original paper language: Russian
Citation:
A. N. Tevyashova, E. N. Olsufyeva, M. N. Preobrazhenskaya, “Design of dual action antibiotics as an approach to search for new promising drugs”, Russian Chem. Reviews, 84:1 (2015), 61–97
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\paper Design of dual action antibiotics as an approach to search for new promising drugs
\jour Russian Chem. Reviews
\yr 2015
\vol 84
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\pages 61--97
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Linking options:
https://www.mathnet.ru/eng/rcr4029
https://doi.org/10.1070/RCR4448
https://www.mathnet.ru/eng/rcr/v84/i1/p61
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